Granulocyte Transfusions

Granulocyte Transfusions

PEP Topic 
Prevention of Infection: Transplant
Description 

Granulocytes, a type of white blood cell, may be obtained from donors via apheresis or from the separation of component parts of standard blood donation.  Granulocyte transfusion is the administration of ABO matched granulocytes.  Granulocyte transfusion has been examined in patients with cancer, particularly those undergoing hematopoietic cell transplantation, for the prevention or treatment of infection.

Effectiveness Not Established

Research Evidence Summaries

Mousset, S., Hermann, S., Klein, S. A., Bialleck, H., Duchscherer, M., Bomke, B., . . . Martin, H. (2005). Prophylactic and interventional granulocyte transfusions in patients with haematological malignancies and life-threatening infections during neutropenia. Annals of Hematology, 84, 734–741.

10.1007/s00277-005-1055-z
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Study Purpose:

To describe one organization’s experience and findings with the use of prophylactic and interventional granulocyte infusions.

Intervention Characteristics/Basic Study Process:

Two different approaches with granulocyte transfusions were used: (1) as an intervention for patients with progressive life-threatening infections and (2) to prevent the recurrence of infections in patients at high risk, including those undergoing allogeneic peripheral stem cell transplant. Patients receiving prophylactic treatment were scheduled for granulocyte transfusion from the beginning of neutropenia in the treatment cycle.  As an intervention, transfusions were given to patients with an absolute neutrophil count (ANC) less than 100/mm3 if they had a life-threatening infection despite other prophylactic antimicrobial treatment or severe infections during a previous neturopenic period, with a high risk of recurrence.  Timing and frequency of granulocyte transfusions were not described, but it was stated that transfusions were stopped if the ANC was greater than 500/mm3 48 hours after the last transfusion.  Outcomes were evaluated 30 days after the first transfusion.

Sample Characteristics:

  • Sixty-seven patients (79% male, 21% female) were included. 
  • Median age was 56 years in the prophylactic group and 52 years in the interventional group (range 21–68).
  • All patients had leukemia or non-Hodgkin lymphoma; 42% were undergoing transplant, 27% were receiving consolidation chemotherapy, and 24% were receiving salvage chemotherapy. Seventy-six percent of patients had a previous underlying fungal infection.

Setting:

  • Single site  
  • Inpatient  
  • Germany

Phase of Care and Clinical Applications:

Patients were undergoing the active antitumor treatment phase of care.

Study Design:

 This was a descriptive observational study.

Measurement Instruments/Methods:

European Organization for Research and Treatment of Cancer (EORTC) criteria for the classification of fungal infections

Results:

  • Twelve percent of patients died with an inability to control infection.  
  • In 82% of the treatment cycles, there was a positive response, and benefit seemed to be greater in the case of fungal infections, with prophylactic use (p = 0.01).
  • Transfusions were reported to be well tolerated.

Conclusions:

This study described the use of granulocyte transfusions and findings between prophylactic and interventional use related to fungal infections.

Limitations:

  • Small sample (<100)
  • Risk of bias (no control group, no blinding, no random assignment) 
  • Unintended interventions or applicable interventions that would influence results were not described.*
  • Selective outcomes reporting*
  • Measurement/methods were not well described.

* Results reporting provides individual case details but little analysis of results and only analysis of difference between prophylactic use and interventional use in a small subset of patients who developed fungal infections.  There was no information regarding antifungal prophylaxis or other aspects of care that can be expected to affect these outcomes.  Reporting of percentages varied between the sample percent, cycles, or episodes of transfusion.  Many of the cases reported as fungal infection were actually possible rather than actual according to the EORTC criteria used. There was no subgroup analysis between various sample groups with different infection risks.

Nursing Implications:

This study provided minimal information; it described an experience in using granulocyte transfusions.

Oza, A., Hallemeier, C., Goodnough, L., Khoury, H., Shenoy, S., Devine, S., . . . Adkins, D. (2006). Granulocyte-colony-stimulating factor-mobilized prophylactic granulocyte transfusions given after allogeneic peripheral blood progenitor cell transplantation result in a modest reduction of febrile days and intravenous antibiotic usage. Transfusion, 46, 14–23.

10.1111/j.1537-2995.2005.00665.x
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Study Purpose:

To compare the clinical outcomes between allogeneic peripheral blood stem cell (PBSC) recipients who did and did not receive matched granulocyte transfusions.

Intervention Characteristics/Basic Study Process:

Patients who did not have an ABO matched donor were assigned to a comparison control group, and those with a matched donor were assigned to receive granulocyte transfusions.  Patients received conditioning either with total body irradiation, etoposide and cyclophosphamide or busulfan and cyclophosphamide given over seven days, or the regimen of total body irradiation and cyclophosphamide administered over three days.  Posttransplant granulocyte colony-stimulating factor was given to all patients on day 1 until neutrophil recovery.  No prophylactic antibacterial or antifungal antibiotics were given.  Prophylactic acyclovir was given to prevent herpes simplex infection.  Empiric antibiotic therapy was given for an initial fever of 38.3°C or higher.  Empiric therapy of amphotericin B was given for persistent fever.

Sample Characteristics:

  • One hundred fifty-one donor-recipient pairs were included.
  • Mean age was 44.5 years (range 14–68).
  • Of the patients included, 56.3% were male and 43.7% were female.
  • The majority of patients had leukemia, myelodysplastic syndrome, myelofibrosis, or aplastic anemia.

Setting:

  • Single site  
  • Inpatient  
  • United States

Phase of Care and Clinical Applications:

Patients were undergoing the active antitumor treatment phase of care. 

Study Design:

This was a prospective two-group study.

Measurement Instruments/Methods:

  • Onset of neutropenia (defined as absolute neutrophil count [ANC] decrease to 500/mm3)
  • Recovery (defined as the first day after ANC nadir that ANC increased to 500/mm3 for three consecutive days)
  • A febrile day (defined as any day during hospitalization with a temperature of 38.3°C or higher)
  • Bacteremia included culture-proven systemic blood infections.

Results:

Patients receiving granulocyte transfusion had a mean of 13.2 days of hospitalization, compared to 29.6 days in the control group (p = 0.03).  Patients receiving transfusions had fewer days of severe neutropenia.  This difference was 1.5 days on average (p = 0.0005).  The percentage of patients who developed fever during hospital stay from the start of conditioning to discharge was 82.7% in patients who did not receive granulocytes versus 64.2% in those who received granulocyte transfusions (p = 0.03). There were no other differences between groups in bacteremia or overall survival.

Conclusions:

Granulocyte transfusions in this group of patients may have a statistically significant but clinically mild beneficial effect on the duration of neutropenia and hospital stay.

Limitations:

  • Risk of bias (no blinding and no random assignment)  
  • Unintended interventions or applicable interventions not described that would influence results *

* There was no subgroup analysis between those who may have received empiric treatment for fever as described in the study methods; therefore, it is unclear if such treatment influenced the results.  Sample sizes with results reporting tend to vary throughout the report, so it is unclear if this is related to missing data from the retrospective method.

Nursing Implications:

The findings suggested that granulocyte transfusions may have some benefits for allogeneic stem cell transplant recipients; however, this study did not provide strong support for this intervention due to study limitations.  Because these patients did not receive routine prophylactic antibiotic or antifungal treatment, it is not clear what the clinical role of granulocyte transfusion might be in the setting of more aggressive preventive clinical management.

Pham, H. P., Rogoza, K., Stotler, B., Duffy, D., Parker-Jones, S., Ginzburg, Y., . . . Schwartz, J. (2012). Granulocyte transfusion therapy in pediatric patients after hematopoietic stem cell transplantation: a 5-year single tertiary care center experience. Journal of Pediatric Hematology/Oncology, 34, e332–e336.

doi:10.1097/MPH.0b013e3182580d40
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Study Purpose:

To determine the efficacy of granulocyte transfusion in neutropenic pediatric patients after undergoing hematopoietic stem cell transplantation (HSCT).

Intervention Characteristics/Basic Study Process:

A retrospective observational review analysis was performed on all pediatric HSCT recipients between January 2005 and and January 2010 in a single center.

Sample Characteristics:

  • Sixteen patients (56% male, 44% female) were included.
  • Average patient age was 12 years.
  • All patients met the criteria for granulocyte transfusion, including an absolute neutrophil count (ANC) less than 500 cells/mm3, documented bacteria land/or fungal infections, and reasonable hope for bone marrow recovery or engraftment.

Setting:

  • Single site
  • Inpatient 
  • Morgan Stanley Children’s Hospital of New York – Presbyterian – Columbia University Medical Center

Phase of Care and Clinical Applications:

  • Patients were undergoing the active antitumor treatment phase of care. 
  • The study has clinical applicability for pediatrics.

Study Design:

This was a retrospective observational review.

Measurement Instruments/Methods:

Data were analyzed using Fisher exact test for binary outcomes and the 2-tailed t test for continuous outcomes.

Results:

One hundred fifty-three granulocyte transfusions were administered to 16 pediatric HSCT recipients. Patients had bacterial infections (69%), fungal infections (19%), and combined infections (12%). Concurrent infections, mostly bacterial (60%), occurred. One adverse reaction of pulmonary toxicity was reported.  The ANC of the stimulated products was significantly higher compared with the unstimulated products; however, neither the average number of granulocytes transfused by weight nor the outcomes difference were noticed between groups.

Conclusions:

Granulocyte transfusion is safe in neutropenic and infected pediatric patients after HSCT. There was no difference in the outcomes between the groups that received stimulated products and those that received unstimulated products.

Limitations:

  • Small sample (<30)
  • Risk of bias (no control group)
  • Findings were not generalizable.
  • Time effect:  New antibiotics, along with new dosing, develop constantly, and the clinical care/treatment may have been different across the time span (2005–2010) of the study.  The authors did not look at difference in the clearing of infections or the survival between the two groups.  No information was provided regarding the prevalence of alloimmunization nor the compatibility between patients and the granulocyte units.

Nursing Implications:

Recruiting pediatric patients for a randomized, controlled trial continues to be challenging.

Guideline/Expert Opinion

National Comprehensive Cancer Network. (2011). NCCN Clinical Practice Guidelines in Oncology: Prevention and treatment of cancer-related infections [v.2.2011]. Retrieved from https://subscriptions.nccn.org/gl_login.aspx?ReturnURL=http://www.nccn.org/professionals/physician_gls/pdf/infections.pdf

http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#detection
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Purpose & Patient Population:

To provide guidance for clinical practices for the prevention and treatment of infection in patients with cancer.

Type of Resource/Evidence-Based Process:

This resource is a consensus-based guideline.

Phase of Care and Clinical Applications:

Patients were undergoing the active antitumor treatment phase of care.

Guidelines & Recommendations:

The guideline

  • Recommends the consideration of general antibacterial prophylaxis in patients at intermediate and high risk for infection, consideration of antifungal prophylaxis during neutropenia and for anticipated mucosits, and antiviral prophylaxis for intermediate- and high-risk patients.
  • Provides suggestions for specific agents for prophylaxis and treatment in various clinical scenarios.
  • Outlines treatment and diagnostic/assessment approaches for neutropenic fever and specific clinical presentations.
  • Notes that chlorhexidine and sliver sulfadiazine-coated short-term central catheters have been shown to decrease the incidence of catheter colonization and bloodstream infections, but not in patients with hematologic malignancies requiring indwelling catheters for approximately 20 days.
  • Notes that vaccination recommendations for transplantation recipients and their household members should be performed.
  • Recommends the pneumococcal vaccine in asplenic patients.

The National Comprehensive Cancer Network (NCCN) does not currently endorse the use of a vancomycin lock solution for long-term vascular access devices due to concerns about the emergence of bacterial resistance if widely used. Influenza vaccination with a vaccine that does not use live attenuated organisms can be safely given, and the guideline recommends administration at least two weeks before receiving cytotoxic therapy.

Limitations:

This study lacked high-quality evidence, with most recommendations being based on consensus.

Nursing Implications:

This guideline provided comprehensive references to assess patient risk of infection and expert recommendations regarding interventions aimed at the prevention and treatment of infection in patients with cancer. The guideline does not discuss long-term survivorship issues in this area.


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